7-100572697-C-T

Variant names:

• chr7-100572697-C-T
• rs546546962
• NM_001348680.2:c.566G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001348680.2(SAP25):​c.566G>A​(p.Arg189Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,535,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R189P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.74
• Publications: 1 publications found

Genes affected

SAP25 (HGNC:41908): (Sin3A associated protein 25) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000274272 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014096469).
• BP6: Variant 7-100572697-C-T is Benign according to our data. Variant chr7-100572697-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2522909.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348680.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP25	NM_001348680.2	MANE Select	c.566G>A	p.Arg189Gln	missense	Exon 5 of 6	NP_001335609.1	A0A087WYF9
	SAP25	NM_001168682.3		c.545G>A	p.Arg182Gln	missense	Exon 5 of 6	NP_001162153.2
	SAP25	NM_001348677.2		c.272G>A	p.Arg91Gln	missense	Exon 4 of 5	NP_001335606.1	Q8TEE9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP25	ENST00000622764.3	TSL:5 MANE Select	c.566G>A	p.Arg189Gln	missense	Exon 5 of 6	ENSP00000481773.2	A0A087WYF9
	SAP25	ENST00000538735.5	TSL:3	c.272G>A	p.Arg91Gln	missense	Exon 5 of 6	ENSP00000442339.1	Q8TEE9
	SAP25	ENST00000614631.4	TSL:2	c.272G>A	p.Arg91Gln	missense	Exon 4 of 5	ENSP00000481351.1	Q8TEE9

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 5 AN: 138674 AF XY: 0.0000538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000948

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000540

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 33 AN: 1383490 Hom.: 0 Cov.: 32 AF XY: 0.0000308 AC XY: 21 AN XY: 682774

African (AFR) AF: 0.00 AC: 0 AN: 31554

American (AMR) AF: 0.0000844 AC: 3 AN: 35562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25130

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35722

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34492

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5688

European-Non Finnish (NFE) AF: 0.0000223 AC: 24 AN: 1078272

Other (OTH) AF: 0.0000519 AC: 3 AN: 57858

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41492

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.056
DANN	Benign	0.77
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-4.7
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.015
Sift	Benign	0.48	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.040
MutPred		0.20		Gain of sheet (P = 0.1208)
MVP		0.014
ClinPred		0.024	T
GERP RS		-9.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.060
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs546546962; hg19: chr7-100170320;